Effect of cyclooxygenase inhibition on brain cell membrane lipid peroxidation during hypoxia in newborn piglets

To test the hypothesis that indomethacin, an inhibitor of cyclooxygenase, reduces free radical-induced brain cell membrane changes during cerebral hypoxia, we determined levels of brain cell membrane lipid peroxidation products and Na⁺,K⁺-ATPase activity as indicators of free radical production and membrane function, respectively, in 29 newborn piglets divided into 4 groups. Eight saline-and 4 indomethacin-treated normoxic animals served as controls; 8 saline-pretreated piglets and 9 piglets pretreated with indomethacin were exposed to hypoxic hypoxia for 60 min. Cerebral hypoxia was documented using³¹P-NMR spectroscopy. In saline-pre-treated hypoxic animals Na⁺,K⁺-ATPase activity decreased significantly and levels of membrane lipid peroxidation products increased significantly compared to normoxic controls. Indomethacin pretreatment prevented the hypoxia-induced increase in membrane lipid peroxidation products but had no effect on the decrease in Na⁺,K⁺-ATPase activity. Thus the apparent reduction in free radical production by indomethacin pretreatment did not prevent the hypoxia-induced change in Na⁺,K⁺-ATPase activity.